Throughout this application various publications are referred to in parentheses. Full citations for these references may be found at the end of the specification. The disclosures of these publications are hereby incorporated by reference in their entirety into the subject application to more fully describe the art to which the subject invention pertains.
Radiation-induced pulmonary syndrome (RIPS) is a delayed lethal event from accidental or intentional exposure to irradiation in case of nuclear accidents or terrorism. In the event of a nuclear accident or deliberate attack resulting in a large population exposure to ionizing radiation, victims will need to be triaged according to the severity of acute radiation illness. Radiation-induced bone-marrow syndrome and gastrointestinal (GI) syndrome occur at lower doses of radiation and have an earlier onset than does radiation-induced pulmonary syndrome. Although acute lung injury is not an early event compared to radiation-induced gastrointestinal and hematologic disorder, successful treatment of gastrointestinal and hematologic syndromes do not rescue patients completely as mortality from respiratory distress at late time point is always an issue. Furthermore, many victims at risk for development of chronic injury will not be symptomatic for months to years after exposure. Therefore, it is necessary to develop a therapeutic strategy that is effective when delivered after the onset of symptomatic injury. Radiation-induced acute lung injury results from a combination of direct cytocidal effects on pneumocytes, generation of free radical and development of sepsis.
Two phases of radiation lung injury have been described. Acute radiation pneumonopathy (pneumonitis) can occur from several weeks to 6 months post-irradiation. If a large volume of lung has been affected, this phase can be life threatening. In late radiation-induced lung injury, occurring months to years after irradiation, the number of inflammatory cells decreases and deposition of collagenous occurs, resulting in irreversible lung fibrosis.
The present invention addresses the need for methods for therapy of subjects for radiation-induced pulmonary syndrome, as well as other pulmonary diseases.